(OR18-04-23) The Role of Riboflavin in Endothelial Function

Objectives: Endothelial cells are critical modulators of vascular tone and interface with systemic circulation. Riboflavin regulates redox reactions and energy metabolism as flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). FAD/FMN are required for the formation of vasodilatory nitric oxide (NO) by endothelial nitric oxide synthase (eNOS). Therefore, riboflavin may play a role in endothelial NO production and vascular homeostasis. The objective of this study was to determine the role of riboflavin in vascular endothelial function.

Methods: Male and female littermate C57BL/6J mice were fed a control diet (6 mg riboflavin/kg) or a riboflavin-deficient diet (1mg riboflavin/kg) from weaning for 8 weeks (n=6 mice/sex/diet/genotype) followed by collection of serum and aorta. Aortic rings were assessed on a wire myograph to determine endothelial-dependent and -independent function.

Results: Mice fed the riboflavin-deficient diet had lower serum riboflavin concentrations (p < 0.05); no differences in serum total homocysteine concentrations were observed. Male riboflavin-deficient mice had impaired (p=0.09) endothelial-dependent relaxation in response to acetylcholine (with ibuprofen, to block prostacyclin vasodilation) compared to control male mice. Incubation of rings with 20nM riboflavin improved endothelial-dependent relaxation in riboflavin-deficient (p < 0.05) and control (p=0.09) male mice. Riboflavin-deficient male mice had lower basal NO production, determined by treating rings with the NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). In contrast, maximal endothelial-dependent relaxation was greater (p≤0.05) in riboflavin-deficient female mice compared to control female mice. There was no effect of riboflavin deficiency on basal NO production in female mice.

Conclusions: These findings suggest a sex-specific effect of riboflavin deficiency on vascular endothelial function. In male mice, riboflavin deficiency is associated with endothelial dysfunction and impaired basal aortic NO production. In female mice, riboflavin deficiency is associated with improved endothelial function, suggesting a compensatory response.

Funding Sources: This research is funded by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.